We propose a phase-I dose-escalation study of intra-articular pNGVL-TK plasmic DNA followed by systemic ganciclovir (hereafter referred to as TK/GCV) for treatment of active rheumatoid synovitis of the knee. We propose to study 4 doses of pNGVL-TK plasmid DNA over a range of one and on-half logs (0.3 mg, 1.0 mg, 3.3 mg, 10.0 mg). A constant dose of intravenous ganciclovir (5 mg/kg twice daily for 3 days) will be used for each dose of pNGVL-TK plasmid DNA tested. We propose to study 2 patients at each dose of pNGVL-TK plasmic DNA, a total of 8 patients.